BiDil: A Case Study of Racial Medicine

History

To fully understand the
controversy over BiDil, one must understand the history and context of its
development, approval, and marketing. In the 1980s, the Veterans Administration
conducted a pair of revolutionary studies (named Vasodilator Heart
Failure Trials (V-HeFt I and II)) on the treatment of heart failure, finding that a
combination of two generic drugs, hydralazine and isosorbide dinitrate (H/I), had
significant, beneficial effects on the conditions of heart failure (Cohn, 1986).[1]
V-HeFT I was randomized, multicenter, double-blind, and
placebo-controlled, tracing 642 men for about 2.3 years. V-HeFT I
included approximately 451 white participants and 180 black
participants, of which 132 white and 49 black participatns received H/I
pills rather than a placebo (Ellison et al., 2008).
V-HeFT II was not a placebo-controlled study, but rather compared the
H/I drug's effectiveness to that of the ACE-inhibitor enalapril heart
treatment. V-HeFT II, therefore, studied the effects of the H/I
combination on 109 black participants and 282 white participants
(Ellison, et al., 2008).

In 1987, V-HeFT leading cardiologist Jay Cohn submitted a “methods” patent for
the H/I combination treatment. This patent guaranteed (it expired in 2007) Cohn
the exclusive rights to market the H/I combination for the specific purpose of
treating heart failure, but, unlike a “combination of matter” patent, it did
not hinder companies from developing and marketing generic combinations of the
drug. Cohn’s 1987 methods patent was not race-specific – it professed the H/I
combination to be a suitable treatment for heart failure with neither an
affirmative nor an exclusionary mention of any races (Sankar and Kahn, 2005).

Cohn’s licensed his patent on the H/I combination to
North Carolina based pharmaceutical company Medco. The company ran
bioequivalence tests on their generic version of the H/I combination[2]
until 1997 when Medco submitted a new drug application (NDA) to the FDA (“Medco
Research...,” 1996); again, there was no mention of race. H/I was submitted as
a racially-blind treatment. Although it deemed H/I a clinically effective
treatment, the FDA rejected Medco’s NDA on the basis of insufficient statistics
and testing. The NDA had included the V-HeFT data as H/I’s legitimating data,
and they, having been designed almost fifteen years ago as “test of theory”
trials, were not designed to fulfill NDA requirements (Kahn, 2004 and
A-HeFT.org, 2005).

Subsequently, Cohn took his patent back and collaborated
with cardiologist Peter Carson to review the V-HeFT data again, only this time,
by race, a factor that had been irrelevant in the initial application for H/I’s
NDA approval. In 1999, the two scientists published a paper claiming
considerable racial variance in response to H/I, a claim supported by the responses
of 158 (49 from V-HeFt I and 109 from V-HeFt II) African Americans that participated in the V-HeFT I (Carson,
1999). Cohn’s patent was then licensed to Massachusetts based pharmaceutical
NitroMed, and, in 2000, Cohn and Carson secured a race-specific methods patent
that provided them exclusive rights to market H/I to treat heart failure in
African Americans only. In 2001, the FDA notified NitroMed that BiDil was
ultimately viable, if confirmatory trials in African Americans could be
satisfactorily completed.

Thus, NitroMed raised the private capital necessary to
launch the African American Heart Failure Trial (A-HeFT). The study included
approximately 1,000 African American individuals of either class III or IV
heart failure (Taylor et al., 2004). Participants (still on their current heart
medication) were randomly separated into two groups; one group received a
placebo and the other took BiDil. After just a year of trial, the study was
suspended. At that time, participants on BiDil experienced a 33 percent reduction
in first hospitalization resulting from heart failure and a 43 percent decrease
in the rate of death (Taylor et al., 2004). Thus, it was declared by the Data
Safety Monitoring Board that keeping some participants on a placebo pill was
unethical (Pihl-Carey, 2004).

Following the trials, an amended NDA was submitted to the
FDA, and BiDil was approved in 2005 for prescription only to African Americans
for the purposes of treating heart disease. NitroMed owns exclusive marketing
rights until 2020, and the race-specific methods patent “prevents insurers from
recommending to doctors that they use generic substitutes to save money”
(Sankar and Kahn, 2005) because BiDil was “tested in doses not available for
its generic components” (Ibid.). Vigilante was hired to do the marketing and
advertising component, and BiDil was priced at approximately $1.80 per pill, or
$10 per day (Medical News Today, 2005). The drug has not been widely prescribed
as it is expensive and poorly marketed (Kahn, 2010). It remains the only
race-specific medicine on the market thus far and is consumed in controversy.

[2]
When a company creates a generic version of a drug or drug combination, like
Medco did with the H/I treatment, it must run bioequivalence tests, tests that
verify that the generic version of the drug functions the same as the original
version (Silverman, 2007).

Figure 2: FDA Logo

The FDA denied BiDil's original New Drug Application on the Basis of insufficient data.

Figure 3: Scientific Research

BiDil researchers manipulated fifteen year old data to reflect
significant difference in response to BiDil amongst 158 African
American participants.